scholarly journals Incidences ofPseudomonas aeruginosa-Associated Ventilator-Associated Pneumonia within Studies of Respiratory Tract Applications of Polymyxin: Testing the Stoutenbeek Concurrency Postulates

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
James C. Hurley

ABSTRACTRegimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences ofPseudomonas-associated ventilator-associated pneumonia (PsVAP). Studies of various interventions other than topical polymyxin (nonpolymyxin studies) served to provide additional points of reference. The PsVAP incidences within the component groups of all studies were benchmarked against groups from observational studies. This was undertaken by meta-regression using generalized estimating equation methods. Dot plots, caterpillar plots, and funnel plots enable visual benchmarking. The PsVAP benchmark (and 95% confidence interval [CI]) derived from 102 observational groups is 4.6% (4.0 to 5.3%). In contrast, the mean PsVAP within NCC polymyxin intervention groups (1.6%; CI, 1.0 to 4.5%) is lower than that of all other component group categories. The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.

2013 ◽  
Vol 57 (9) ◽  
pp. 4524-4531 ◽  
Author(s):  
James C. Hurley

ABSTRACTAmong various methods for preventing ventilator-associated pneumonia (VAP), the evidence base for selective digestive decontamination (SDD) appears most compelling. However, the extent ofStaphylococcus aureusemergence with SDD use remains uncertain. Groups from 37 observational studies and component (control and intervention) groups from 58 studies of SDD and other methods of VAP prevention were sourced exclusively from 10 systematic reviews.S. aureusas a proportion of VAP isolates (S. aureusisolate proportion [S. aureusIP]) among component groups was calibrated versus that among observational groups (the benchmark). The influence of topical placebo used for blinding purposes and other group-level factors was estimated using generalized estimating equation methods (GEE). The meanS. aureusIP is 22% (95% confidence interval [CI], 19 to 25) for 37 observational groups versus 32% (24 to 41) and 20% (15 to 25) for 22 control groups from the SDD evidence base which did versus did not receive topical placebo, respectively. In GEE models including all 148 observational and component groups, membership of a control (P= 0.03) or intervention (P< 0.001) group of an SDD study that used topical placebo was associated with higherS. aureusIP, whereas, in contrast, membership of these groups was without effect onPseudomonas aeruginosa. Topical placebo is implicated as a vehicle for selective cross-infection withS. aureuswithin the specific context of the SDD evidence base. This effect of topical placebo is perfidious; it could contribute to the higher VAP incidence and inflate the apparent “effectiveness” of SDD. The SDD evidence base requires reappraisal.


2018 ◽  
Vol 5 (11) ◽  
Author(s):  
James C Hurley

Abstract Background Topical polymyxin (PM)–based regimens to decolonize patients receiving prolonged mechanical ventilation (MV) have been widely studied. However, paradoxical bacteremia incidences remain unexplained. Methods The literature was searched for studies of topical PM–based regimens used to decontaminate MV patients reporting incidences of overall and Pseudomonas bacteremia data. In addition, observational groups without any intervention and trials of various interventions other than topical PM (non-PM studies) served to provide external benchmarks and additional points of reference, respectively. The bacteremia incidences were extracted from the control and intervention (component) groups of these studies and compared with metaregression using generalized estimating equation methods. Results The summary odds ratio derived from studies of topical PM–based interventions against overall bacteremia was 0.60 (95% confidence interval [CI], 0.53–0.69). Benchmark incidences per 100 MV patients for overall (mean, 8.9%; 95% CI, 6.9% to 10.9%) and Pseudomonas (mean, 0.7%; 95% CI, 0.5% to 1.1%) bacteremia were derived from 16 observational studies. By contrast, among 17 studies of topical PM, the mean incidences among control groups for overall (mean, 15.3%; 95% CI, 11.5% to 20.3%) and Pseudomonas (mean, 1.6%; 95% CI, 0.9% to 3.1%) bacteremia were both higher, whereas these incidences in the intervention groups for both topical PM and non-PM studies were in each case more similar to the respective benchmarks. These paradoxical incidences cannot readily be explained in metaregression models. Conclusions Paradoxically, despite an apparent prevention effect of topical PM–based methods against bacteremia overall, the incidences of Pseudomonas bacteremia within the component groups of these studies are unusually high vs literature-derived benchmarks.


Author(s):  
Ismi Masyithah ◽  
Usman Hadi ◽  
Eko Budi Koendhori

Introduction: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infections in the intensive care unit (ICU). Mechanically, ventilated patients have a higher risk of VAP. VAP can increase morbidity, mortality, and treatment costs. However, Indonesia lacks data about VAP. The objective of this study was to find out the characteristics of VAP in Dr. Soetomo General Hospital, Surabaya, in the period of August 2017 until August 2018.Methods: This was a cross-sectional study by assessing medical records of the patients in ICU. The variables observed in this study were age, gender, outcome, length of stay in the ICU (LOSICU), and primary diagnosis. The inclusion criteria were the patients who have been using mechanical ventilation at least 2 x 24 hours in the ICU and confirmed VAP. The data were analyzed descriptively by using Microsoft Excel 2016.Results: A total of 18 VAP patients were diagnosed. VAP patients were dominated male (55.6%). The mean of LOSICU was 22.83 ± 11.24 days, and the mortality rate of VAP patients was high (55.6%). 30% of VAP patients had Guillain-Barre Syndrome (GBS) as the primary diagnosis, and 16.65% had Congenital Heart Disease (CHD).Conclusion: Most VAP patients were male and had prolonged stays. The mortality rate of VAP patients was still high. GBS was the most frequent of primary diagnoses in patients with VAP and also CHD.


Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1027
Author(s):  
James C. Hurley

There are several antiseptic, antibiotic and non-decontamination-based interventions for preventing intensive care unit (ICU) acquired infection. These have been evaluated in >200 studies. Infection prevention using topical antibiotic prophylaxis (TAP) appears to be the most effective. Whether antibiotic use in the ICU may influence the risk of infection among concurrent control patients within the same ICU and result in asymmetrical herd effects cannot be resolved with individual studies examined in isolation. The collective observations within control and intervention groups from numerous ICU infection prevention studies simulates a multi-center natural experiment enabling the herd effects of antibiotics to be evaluated. Among the TAP control groups, the incidences for both ventilator associated pneumonia (VAP) and mortality are unusually high in comparison to literature-derived benchmarks. Paradoxically, amongst the TAP intervention groups, the incidences of mortality are also unusually high and the VAP incidences are similar (i.e., not lower) compared to the incidences among studies of other interventions. By contrast, the mortality incidences among the intervention groups of other studies are similar to those among the intervention groups of TAP studies. Using topical antibiotics to prevent infections acquired within the ICU environment may result in profoundly asymmetrical effects.


2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Antoine Guillon ◽  
Delphine Fouquenet ◽  
Eric Morello ◽  
Clémence Henry ◽  
Sonia Georgeault ◽  
...  

ABSTRACTThe endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia. The bacteria present in the biofilm are more resistant to antibiotics, and current medical practices do not make it possible to eliminate.Pseudomonas aeruginosais one of the leading pathogens that cause biofilm infections and ventilator-associated pneumonia. Poly-l-lysine (pLK) is a cationic polypeptide possessing antibacterial properties and mucolytic activity by compacting DNA. Here, we explored the antibiofilm activity of pLK to treatP. aeruginosabiofilms on ETTs while taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicates aP. aeruginosabiofilm formedin vitroon 96-well microplates. We further demonstrated that pLK alters bacterial membrane integrity, as revealed by scanning electron microscopy, and eventually eradicates biofilm formed either by reference or clinical strains ofP. aeruginosabiofilms generatedin vitroon ETTs. Second, we collected the ETT from patients withP. aeruginosaventilator-associated pneumonia. We observed that a single dose of pLK is able to immediately disrupt the biofilm structure and kills more than 90% of bacteria present in the biofilm. Additionally, we did not observe any lung tolerance issue when the pLK solution was instilled into the ETT of ventilated pigs, an animal model particularly relevant to mimic invasive mechanical ventilation in humans. In conclusion, pLK appears as an innovative antibiofilm molecule, which could be applied in the ETT of mechanically ventilated patients.


1993 ◽  
Vol 69 (04) ◽  
pp. 344-350 ◽  
Author(s):  
B H Chong ◽  
J Burgess ◽  
F Ismail

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.


1966 ◽  
Vol 16 (03/04) ◽  
pp. 752-767 ◽  
Author(s):  
J. R O’Brien ◽  
F. C Path ◽  
Joan B. Heywood ◽  
J. A Heady

SummaryMethods for measuring and comparing day to day differences in the response of platelet aggregation in platelet-rich plasma to added ADP, 5-H.T., adrenaline and collagen are reported. Platelet aggregation induced by ADP, 5-H.T. and adrenaline was studied in patients with acute myocardial infarction and in others 3 months to 5 years after an infarct; some were receiving anti-coagulants and others not: these three groups were compared with three control groups. The mean platelet shape was rounder and the response to ADP and to 5-H.T. and one parameter of the response to adrenaline was significantly greater in all groups of patients with myocardial infarct taken together than in the controls. The platelet-rich plasma from patients with recent infarction were most responsive to ADP and 5-H.T. immediately after the infarct. Anti-coagulants had no effect on these tests. However, there was wide variation within the individuals and much overlap between groups, and these tests can only reliably distinguish between groups and not between individuals. The significance of these findings is discussed.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 68-73 ◽  
Author(s):  
Pierre-Hugues Roche ◽  
Jean Régis ◽  
Henry Dufour ◽  
Henri-Dominique Fournier ◽  
Christine Delsanti ◽  
...  

Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6–71 years). The mean tumor volume was 5.8 cm3 (range 0.9–18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12–50 Gy), delivered with an average of eight isocenters (range two–18). The median peripheral isodose was 50% (range 30–70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12–79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity—related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.


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